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101.
Siim Suutre Alar Toom Andres Arend Gunnar Selstam 《Growth factors (Chur, Switzerland)》2013,31(2):114-120
Transforming growth factor beta isoforms (TGF-β1, TGF-β2, and TGF-β3) most likely play a role in bone physiology, but little is known about their relative importance in normal as well as in heterotopic bone. This study focused on possible differences in the localization and relative content of different TGF beta isoforms in heterotopic ossifications (HO) by comparing HOs, which have developed less than 17 months (immature HOs) with those developed 3–9 years (mature HOs). The HOs were harvested after total hip arthroplasty (THA) during revision surgery. The HO samples were decalcified, embedded in paraffin and sectioned. Azan staining was used to evaluate histological structure of the ossifications and immunohistochemical analysis was performed to estimate the localization of three TGF beta isoforms in the HOs. Comparison of different TGF beta isoforms in the immature and the mature ossifications showed that the content of TGF-β2 was decreased by almost three times in the mature HO as compared to the immature HO (p = 0.0064). The proportions of other isoforms in HOs did not differ significantly. This study shows that the relative importance of TGF betas change with HO development. 相似文献
102.
Mutations in leucine rich repeat kinase 2 (LRRK2) are a major cause of familial Parkinson's disease (PD) and a risk factor for its sporadic form. LRRK2 hyperactivity has also been reported in sporadic PD, making LRRK2 an appealing target for PD small-molecule therapeutics. At a cellular level, increasing evidence suggests that LRRK2 regulates membrane trafficking. Under some conditions LRRK2 also associates with microtubules, the cellular tracks used by dynein and kinesin motors to move membranes. At a structural level, however, relatively little was known about LRRK2. An important step toward bridging this gap took place last year with the publication of structures of LRRK2's cytosolic and microtubule-bound forms. Here, we review the main findings from these studies and discuss what we see as the major challenges going forward with a focus on areas that will require structural information. We also introduce the structural techniques—cryo-electron microscopy and cryo-electron tomography—that were instrumental to solving the structures of LRRK2. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society 相似文献
103.
Marco Romano Monica Sen Cristiano Scottà Rowa Y. Alhabbab Andres Rico-Armada Robert I. Lechler Michael Burch Giovanna Lombardi 《European journal of immunology》2021,51(8):2086-2092
Regulatory T-cells (Tregs) are a subset of T cells generated in the thymus with intrinsic immunosuppressive properties. Phase I clinical trials have shown safety and feasibility of Treg infusion to promote immune tolerance and new studies are ongoing to evaluate their efficacy. During heart transplantation, thymic tissue is routinely discarded providing an attractive source of Tregs. In this study, we developed a GMP-compatible protocol for expanding sorted thymus-derived CD3+CD4+CD25+CD127– (Tregs) as well as CD3+CD4+CD25+CD127–CD45RA+ (RA+Tregs) cells. We aimed to understand whether thymic RA+Tregs can be isolated and expanded offering an advantage in terms of stability as it has been previously shown for circulating adult CD45RA+ Tregs. We show that both Tregs and RA+Tregs could be expanded in large numbers and the presence of rapamycin is essential to inhibit the growth of IFN-γ producing cells. High levels of FOXP3, CTLA4, and CD25 expression, demethylation of the FOXP3 promoter, and high suppressive ability were found with no differences between Tregs and RA+Tregs. After freezing and thawing, all Treg preparations maintained their suppressive ability, stability, as well as CD25 and FOXP3 expression. The number of thymic Tregs that could be isolated with our protocol, their fold expansion, and functional characteristics allow the clinical application of this cell population to promote tolerance in pediatric heart transplant patients. 相似文献
104.
Camille Cenni Stephanie Andres Maja Hempel Tim M. Strom Ellen Thomas Angela Davies Norma Timoney Alessandra Frigiola Malcolm Logan Muriel Holder-Espinasse 《European journal of medical genetics》2021,64(7):104213
Holt-Oram syndrome (HOS) is a rare, autosomal dominant heart-hand syndrome caused by mutations in the TBX5 gene. A wide spectrum of TBX5 mutations have been reported previously, most resulting in a null allele leading to haploinsufficiency. TBX5 gene duplications have been previously reported in association with typical and atypical HOS phenotypes. Ulnar-Mammary syndrome (UMS) is a distinct rare, autosomal dominant condition caused by mutations in the TBX3 gene. TBX5 and TBX3 are physically linked in cis on human chromosome 12 and contiguous chromosome 12q24 deletions comprising both TBX5 and TBX3 genes have been previously reported but to our knowledge, duplications have never been described. We report on a large German family with at least 17 affected individuals over 6 generations bearing a duplication at 12q24.21 identified on array-CGH comprising both TBX5 and TBX3 genes. Affected patients are presenting with HOS and UMS symptoms, consisting of variable limb anomalies involving the radial and the ulnar rays and cardiac findings such as congenital heart defects, persistent arterial duct or aortic stenosis, and non-classical symptoms, such as supernumerary nipples and cardiomyopathy. Fluorescence in situ hybridisation confirmed a tandem duplication at the 12q24.21 locus. This is the first report of a contiguous TBX3/TBX5 duplication associated with HOS/UMS phenotype. 相似文献
105.
Andres Torres Kathleen Lerut Paul Lambrechts Reinhilde Jacobs 《Journal of endodontics》2021,47(1):133-139
Guided endodontics has been used for the treatment of anterior teeth with a successful outcome. This approach is not only limited to anterior teeth because it can also be used for the treatment of premolars and molars. However, in such cases, space may be a limitation because a long bur has to be used in addition to the guide being placed on top of the teeth. The aim of this case report was to present a novel guided endodontics technique using a sleeveless 3-dimensional–printed guide. This design can reduce vertical space, allowing an open view of the tooth and irrigation during drilling. A 46-year-old female patient consulted the endodontic department with intermittent pain around tooth #5. Tooth #5 presented pain upon percussion and responded negative to a cold test. The initial periapical radiograph revealed an apical radiolucency with pulp canal obliteration. Clinically, there was no sinus tract. The tooth was diagnosed with pulp necrosis and symptomatic apical periodontitis. Guided endodontic treatment was performed with a sleeveless 3-dimensional–printed guide and long neck carbide bur with a head diameter of 1 mm to drill a minimally invasive access cavity up to the root canal. A completely healed apical area of tooth #5 was visible after 1 year on periapical radiographs. This technique seems to be a promising alternative in comparison with the conventional guided endodontic guide design for the negotiation of pulp canal obliteration in cases in which vertical space is limited. 相似文献
106.
de Siqueira Fabiana Suelen Figueredo Hilgemberg Bruna Araujo Lucila Cristina Rodrigues Hass Viviane Bandeca Matheus Coelho Gomes João Carlos Reis Alessandra Loguercio Alessandro D Cardenas Andres Felipe Millan 《Clinical oral investigations》2020,24(2):809-822
Clinical Oral Investigations - The aim of this study was to investigate the effects of collagen cross-linking agents on nanomechanical and bonding properties of eroded dentin (ED), 24 h... 相似文献
107.
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109.
Clathrin-mediated endocytosis is required for compensatory regulation of GLR-1 glutamate receptors after activity blockade 下载免费PDF全文
Grunwald ME Mellem JE Strutz N Maricq AV Kaplan JM 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(9):3190-3195
Chronic changes in neural activity trigger a variety of compensatory homeostatic mechanisms by which neurons maintain a normal level of synaptic input. Here we show that chronic activity blockade triggers a compensatory change in the abundance of GLR-1, a Caenorhabditis elegans glutamate receptor. In mutants lacking a voltage-dependent calcium channel (unc-2) or a vesicular glutamate transporter (VGLUT; eat-4), the abundance of GLR-1 in the ventral nerve cord was increased. Similarly, the amplitude of glutamate-evoked currents in ventral cord interneurons was increased in eat-4 VGLUT mutants compared with wild-type controls. The effects of eat-4 VGLUT mutations on GLR-1 abundance in the ventral cord were eliminated in double mutants lacking both the clathrin adaptin protein unc-11 AP180 and eat-4 VGLUT. In contrast, mutations that decreased ubiquitination of GLR-1 did not prevent increased ventral cord abundance of GLR-1 in eat-4 VGLUT mutants. Taken together, our results suggest that GLR-1 is regulated in a homeostatic manner and that this effect depends on clathrin-mediated endocytosis but does not require ubiquitination of GLR-1. 相似文献
110.
MiR‐708‐5p is differentially expressed in childhood acute lymphoblastic leukemia but not strongly associated to clinical features 下载免费PDF全文